Monday, May 28, 2012

How Bad is Fructose? David Despain Interviews Dr. John Sievenpiper

In my article "Is Sugar Fattening?", I discussed a recent review paper on fructose, by Dr. John Sievenpiper and colleagues (1). It was the most recent of several review papers to conclude that fructose is probably not inherently fattening in humans, but that it can be fattening if it's consumed to excess, due to the added calories. Dr. Sievenpiper and colleagues have also written other papers addressing the metabolic effects of fructose, which appear to be fairly minor unless it's consumed to excess (2, 3, 4, 5). The senior author on these studies is Dr. David Jenkins at McMaster University. David Despain, a science and health writer who publishes a nice blog called Evolving Health, recently interviewed Dr. Sievenpiper about his work.

It's an interesting interview and very timely, due to the recent attention paid to fructose in the popular media. This has mostly been driven by a couple of high-profile individuals-- an issue they discuss in the interview. The interview, recent papers, and sessions at scientific conferences are part of an effort by researchers to push back against some of the less well founded claims that have received widespread attention lately.

Let me be clear that I feel strongly that concentrated added sugar is not healthy-- and this isn't exactly a controversial position. Sugar is one of the foods that consistently shows up right before metabolic/cardiovascular/dental health declines dramatically in industrializing cultures. But no one eats plain granulated sugar, because it doesn't taste very good on its own. We add it to other foods, reducing nutritional value and increasing energy density, seductiveness, and palatability. However, none of those problems apply to whole fresh fruit, which is also rich in fructose and has been eaten in quantity by our ancestors for tens of millions of years. So is fructose really the main problem, or is it the overconsumption of low-nutrition refined foods in general*?

Here's Dr. Sievenpiper:

We didn't set out an a priori hypothesis that fructose doesn't do
these things. In fact, our hypothesis would've been "Well, everyone's
talking about it. The animal data is suggestive of an adverse effect of
fructose." If anything, our hypothesis was that there’s going to be an
adverse effect...

We decided to use the gold standard or highest level of evidence in
nutrition or, really, in most fields -- which is controlled trials; and,
in nutrition, is controlled dietary feeding trials. We wanted to apply
the best tools we have, which was systematic review and meta-analyses
tools to synthesize that knowledge and information to try to answer the
question about really.

Is it true? What we found was that it wasn't. We looked at bodyweight -- which is the Annals [of Internal Medicine] data
that you’re aware of -- in each case there was no effect of fructose
when it was isocalorically exchanged. There was no adverse effect on
bodyweight, blood pressure, or uric acid. We do see a very consistent and strong effect on bodyweight when fructose is providing excess energy.

There are a number of interesting points in the interview. One of the most informative for me was when he discussed de novo lipogenesis, or the synthesis of fat from carbohydrate. This process is one of the arguments some people use to suggest carbohydrate is fattening-- fructose is the most efficient substrate for DNL. Putting aside the most obvious problem with this argument for the time being**, it also turns out that even in the case of fructose, only a small percentage of it becomes fat.

* I'm asking this question somewhat rhetorically, but just to be clear my current position is that refined fructose and sugar can be problematic in excess, due to their metabolic effect to increase visceral fat, reduce insulin sensitivity, cause lipid abnormalities, and increase blood pressure. This shows up mostly in studies in which calorie intake increases, but it's important to recognize that subjects in these studies weren't always deliberately overfeeding. They were sometimes inadvertently overfeeding because they weren't naturally compensating for the calories added to the diet via a large amount of fructose or glucose sweetened beverage. Although calorie compensation is poor regardless of whether a beverage is sweetened with fructose or glucose, the fructose beverage has more serious adverse metabolic effects. The practical implication is that if a person adds three sodas to her daily diet, she will end up consuming more total calories and be effectively overfeeding, even if she makes no deliberate effort to eat more calories, and therefore she may in fact suffer some of the adverse effects of excess fructose that only emerge in a hypercaloric context (fat gain, insulin resistance, hypertension, etc.). Eating whole, fresh fruit should not have the same effect because it doesn't lead to overconsumption in the context of a normal mixed diet.

** If fructose is fattening due to its ability to become fat, then dietary fat should be even more fattening because it doesn't have to undergo an inefficient conversion process-- it's already fat.

75 comments:

Please explain the mechanism for action in how dietary fat is stored in fat cells and creates obesity without the presence of excess or even any carb in the diet?

Please start with coconut oil and then move on to others.

I am genuinely curious as without a mechanism I am unable to verify the below statement on my own.

Quote: ** If fructose is fattening due to its ability to become fat, then dietary fat should be even more fattening because it doesn't have to undergo an inefficient conversion process-- it's already fat.

Yes, that statement is a leap too far. You get fat cats and dogs on high-carb chow, not on fatty meat.Surely we all know how fat is stored by now.

A fructose study can miss the combined effect of fructose plus glucose, which is what we are really talking about.

IMHO the difference between healthy and unhealthy fructose use, for mmost people, has to do with timing. Not calories per se. It is the constant sipping and snacking on these foods that stows away fat and builds up metabolic stress.If you ate honey as the Hadza do; 30% of calories, but in an intermittent fasting way - you would be able to burn off both sugar and fat between meals.

Logically white sugar seems benign if eaten in reasonable amounts and if paired with other nutrient dense foods in a cohesive manner.

For example some fruits are naturally more nutrient dense than other fruits and same with other natural foods. Some natural foods are very high in bio-available nutrients like liver, eggs, and milk(especially if skimmed).

Fruit is obviously the best choice because all the nutrients needed are present. Potassium and other nutrients have an insulin like effect.

Sucrose found in fruits is also a better fuel than starch because the fructose and glucose enhance each other and fructose has some beneficial properties glucose does not.

While yes, fat is already fat, it isn't always fat that is meant to be stored in adipose tissue. The fat usually passes through the liver, is transported all over the body in different types of vesicles and will have different fates based on its chain length, unsaturation, and we now know, location of unsaturation. If fat is being made from fructose, the body is most likely in a fed state and is synthesizing fat for the sole purpose of storage. On the other hand, fat does not send the same "fed state" signals, and therefore might not necessarily end up as storage. I think it is the inherent hormonal milieu resulting from the consumption of processed sugar in addition to an increase in calorie consumption, that leads to fructose being "fattening".

This blog helps to formulate a (mostly non-hepatic) mechanism:http://high-fat-nutrition.blogspot.co.nz/2012/05/on-glut5.htmlWhy are "excess" calories more likely to be consumed as sugar? Is it really because the food value goes unrecognised? (low food reward? Low satiety?)

Interestingly there are (apparently) no fat taste receptors, and pure fat is a flavourless texture.

Stephan, thanks for helping to counter the recent demonization of fruits in the Paleo/ancestral blogosphere with your voice of reason, along with that of Denise Minger, Chris Masterjohn and others. I'm hoping you'll do the same for (raw, especially wild, raw) honey some day. Too often I've seen fruits equated with refined and high-heated fructose and honey with refined and high-heated table sugar, as though all foods that contain fructose or sugars of any sort were exactly the same.

There are a number of interesting points in the interview. One of the most informative for me was when he discussed de novo lipogenesis, or the synthesis of fat from carbohydrate. This process is one of the arguments some people use to suggest carbohydrate is fattening-- fructose is the most efficient substrate for DNL. Putting aside the most obvious problem with this argument for the time being**, it also turns out that even in the case of fructose, only a small percentage of it becomes fat.

I may be oversimplifying here, but isn't hepatic DNL something that only happens when the liver's glycogen stores are full? The model I have in my mind is that when the liver gets some fructose, the first thing it tries to do is convert it to glycogen. If the liver's glycogen stores are full, then it has to convert the glucose to fat.

If this is correct, than we should see a threshold offect. Below the threshold there will be minimal DNL, but once you exceed the threshold, all additional fructose will be converted to fat, since there's no other place for it to go.

If you look at this Glut5 paper originally linked by Hyperlipid, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652499/you'll see that as much as half of fructose can be used outside the liver:

"This low fructose level results from rates of intestinal absorption lower than that of glucose and from efficient clearance of blood fructose mainly by the liver (50–70%) and, to a lesser extent, (20%) by the kidneys (103)."

Hunter-gathers are not big fruit eaters, maybe because fruits don't have many calories (probably more useful as a source of water sometimes). But they do love honey.And fructose is in all the roots and tubers that we did evolve to eat. I figure that carbs, though desirable, were relatively rare in our natural diet so we evolved to maximise use of them; and that this is why intakes in excess of the original design parameters override and distort fat utilization.

I think when stephen says "If fructose is fattening due to its ability to become fat, then dietary fat should be even more fattening because it doesn't have to undergo an inefficient conversion process-- it's already fat."

He is saying in the context of over-feeding. If you eat fructose past the point of needed energy than you will store it as fat but the process isn't as efficient as storing fat into fat.

If you over feed fat the same thing happens except the process of turning fat into fat is more efficient than fructose.

@George"Hunter-gathers are not big fruit eaters, maybe because fruits don't have many calories (probably more useful as a source of water sometimes). But they do love honey."

Your comment is correct only if we assume that the hunter gatherers exist only in the colder climates.

Humans evolved in Africa and moved out only over the last 60,000years ago. So majority of our evolution happened in Africa. Your statement is not true of Africa, if you have read that excellent article by Denise Minger.

African Fruits are very sweet and very huge. They do provide substantial calories. Kitavans are known to consume a lot of calories from fruits.

Excess calories even in the absence of carbohydrate still does not allow you to eat above your means. If you eat more fat, you will burn more fat, but also store more fat.

@George Henderson: Yes, pigs are often fattened up with carbs, go and do some research on DNL in rats and animals - it is a pathway that is significantly more active in these species, not so much in humans. Read some of the carb overfeeding studies in humans and you see that the body starts to ramp up carb burning to insanely high levels, even when glycogen is topped out.

@Danielle: Who says you have to be receiving fed state signals to store fat? It is not a biological requirement.

Can you speak to the effect fructose has on oxidative metabolism? I ask because the heightened level of serum (and tissue) carbon dioxide binds to proteins (carbaminos) and alters their structure. Fructose engenders this process to a great extent and I'm wondering if we're missing a factor.

its not the same type of fat that is store in our cells, it is an attempt to further divide the low carb community (LC- which has been highly succesful in control both weight and health). Folks with lots of carbs to sell are fighting back hard. Fear the bread NOT the butter

slightly off topic: Have there been recent industrial advances in fructose production?

Pure crystalline fructose used to sell at quite a premium above sucrose (used to be almost double), but I recently noted this premium's shrunk, like a 20% premium.

On a another off topic side note, I have some pure dextrose (purchased from a wine making shop; can't get it at any of the regular grocery chains any more) and I really can't sense a huge difference in sweetness between the powdered dextrose and fructose.

Is the alleged "much sweeter" sweetness of fructose a genetic thing?

The taste of the fructose seems slower-onset, feels warmer (may be the exothermic heat of dilution?) and lasts a little longer.

> Please explain the mechanism for> action in how dietary fat is stored in> fat cells and creates obesity without> the presence of excess or even any> carb in the diet?

Are you asking after reading Taubes?

In Good Calories, Bad Calories, Gary Taubes asserted that in the absence of dietary carbohydrate the body could not make enough G3P to be able to store dietary fat in adipocytes.

He has withdrawn that assertion. The body does have ways of making as much G3P as it needs even in the face of very low dietary carbohydrate

at 46 minutes in this interview http://www.thelivinlowcarbshow.com/shownotes/3588/gary-taubes-responds-to-critics-episode-439-pt-1/

If you want a long explanation on why he ignored the literature[0] on G3P you can listen to the whole thing.

he changed his story such that low carbohydrate diets still "work" but he's dropped the "cannot store fat without dietary carbs" story.

Maybe some day he can drop the motivated reasoning that prevents him from following the logic through to its conclusion, and drop the motivated reasoning that leads him to ignore or arbitrarily dismiss competing theories, evidence and mechanisms

[0] seemingly he never read it & relied on the interview. Does this explain why he ignored the lit after others publicized it for him?

Clearly the metabolism of fats and sugars is going to be different depending on whether the body is energy sufficient or deficient.

Another factor that needs to be considered is the effect of fructose on gut bacteria, and how that affects wider body metabolism. There is evidence that excess fructose lead to imbalances in gut fauna and metabolism that have wider health consequences.

That effect will be different in those who have a healthy gut bacteria, and those whose gut fauna has already been compromised and become fructose dependent - eg those with fungal infections such as candida which reportedly thrives on fructose.

I hypothesize that such infections are more common than realised in those on the Standard American Diet (SAD), who are also likely to be regular antibiotic consumers. It appears an effect of antibiotics may be to leave space for fungal development.

Some argue that for those with a candida infection fructose is best avoided.

So as usual it is complex - in the healthy fructose in moderation from whole foods is probably a plus - in those with compromised digestion due to a bacterial imbalance or fungal infection fructose consumption may be a distinct negative until the imbalances have been dealt with.

Fructose consumption even as part of whole foods in excess of calorie needs is likely to have negative health influences.

Refined fructose supplied in nutrient deficient or depleted foods is also likely to have a negative long term influence on health.

So at a technical level the message that fructose is a killer is misplaced. For the average person on a SAD, who has high antibiotic exposure and consumes excess calories, on average high fructose consumption in health terms is probably bad news, and is that not the message Dr Ludwig is trying to convey.

The problem is that complex nuanced arguments do not get the same exposure as those that are more direct and easy to understand, if less technically correct. Dr Ludwig has greatly heightened awareness of the fructose issue, and we the general public are in great need of nutritional education so we can make informed choices - so maybe a few more caveats and exceptions in his argument would make his arguments less susceptible to denigration.

The refined food industry needs to sell product, but in the long term will it ultimately maintain it's profitability from customers that are experiencing increasing ill-health, some of which customers are the managers and employees of those same food companies - and that is without considering the wider cost of poor diet to nations in terms of health, social and behavioral impact, and loss of economic output.

@ Fred,I've seen evidence of tropical HGs who have access to fruits and neglect them or disdain them as foods (maybe some proto-Lustig has got to them). See this blog:http://www.archevore.com/panu-weblog/2011/1/5/guest-post-professor-gumby-essay-001.htmlBreadfruit and coconut, while fruits, are starch and fat respectively.I'm not saying HG people never eat them, but that the calories available in sweet fruit are not always exploited as avidly by HG as by moderns, and are sometimes ignored.

For a herding people who say they will only collect fruit as a last resort in famine, after eating their livestock, even though they are going hungry in the present, see the Suri in the TV series Tribehttp://en.wikipedia.org/wiki/Tribe_(TV_series)This series is a great resource for a cross-section of modern HG and nomadic lifestyles.

Tho this may have been one of the related tribes in series 2.The Akie in series 3 were big honey consumers, it seemed to be their main carb.Only the babongo in the episodes of Tribe I've seen ate fruit onscreen and that was a small amount on a hunt; none was collected for later.

What puzzles me about Lustig is that he never mentions copper deficiency. Fructose is known to down-regulate the gut copper transporter Ctr1, and the copper people say this is why fructose is bad for you. It's really only bad if you already have copper deficiency. Of course, the copper people also say most of us do have copper deficiency, although the Powers That Be are convinced we don't. The PTB were utterly destroyed by the recent finding that non-alcholic fatty liver disease is linked to copper deficiency, but as yet they don't seem to have noticed.

A key question is how much sugar is too much? To be fair to Robert Lustig, although he perhaps overstates his case for sugar being a poison, he is right that we consume way too much of it, and because fructose is very sweet, it is especially likely to be overconsumed because it is added to soft drinks and desserts by food manufacturers. But as far as the dose goes, how much should we be consuming? It might make an interesting post for you Stephan. Based on the research, what is the most sugar a person should eat in a day or a week if they want to remain healthy?

I would have to agree that fruit causes fat in larger quantities. When my daughter went through a growth spurt between 16 and 18 months, we happened to have an abundance of fresh organic fruits. She was hungry constantly so I reached for the fruits to hold her off until I could prepare something more substantial. She ended up getting probably 3-4 pieces of fruit a day, which is a ton for a toddler! What was I thinking!? Her height to weight ratio went way off and I've been kicking myself ever since.

Regarding the candida issue: it may seem that the logical thing to do would be to reduce its food supply in order to weaken or kill it. However there is a German study that I saw quoted (which I am looking for, so I can't post source yet) that says this causes the Candida to go systemic since it now has to seek sugar elsewhere (like in our bloodstream).

Come to think of it, I know people who have been on a sugar-free candida diet for years and are still struggling with it.

which blog backs up your comments ^ that a low carb diet is not necessarily the solution / or risks introducing other deficiencies which compromise wider health and immune function.

All of which begs questions as to long term health effects of our best modern interpretation of very strict low carb 'Paleo' diets.

Unlike preagriculatural populations we do not have the dietary wisdom garnered from generation of observation . . .in the form of the knowledge of a basket of foods required for health based on the foods available in the natural environment, e.g. for artic dwellers including part digested food from reindeer guts, pine needles tea . . .

And all that is before our extensive efforts, and considerable successes in adulterating the entire food chain in the well-meaning pursuit for cheap food, but without adequate knowledge or consideration of the long term health consequences, and potential social consequences of on balance a sicker and less intelligent, less empathetic, more aggressive, more acquisitive global population.

"No major differences in mineral balances were evident between the two groups during the pretest study when the subjects ate self-selected diets. In contrast, when fed the test diets, the group consuming the low-Cu fructose diet had significantly more positive balances for all minerals studied than the group fed the low-Cu cornstarch diet. The results indicate that dietary fructose enhances mineral balance."http://www.ajcn.org/content/49/6/1290.abstract

I think where people get the idea that fructose increases need for copper comes from rat studies but when you look at human studies like the one posted by key and this one http://www.ajcn.org/content/42/2/242.short you see it increases copper balance compared to starch.

@Key and CliffYes, mineral balance is enhanced, because fructose binds metals and increases their absorption. But copper-dependent SOD activity is lower. So by one measure copper status is better, but by the measure that really matters, it's worse.

I love biochemistry. My main hobby is to weed though all of these "experts" blogs, lectures, etc.. and understand how biochemical processes have evolutionary implications. I am not on board with strict low carb, nor do I view carbs and sugar as safe substances in certain situations.

In a nut shell, calories should be thought of as effectors of hormonal signaling that lead to downstream changes in the gene expression patterns of the cells. With this in mind, different classes of calories all lead to various downstream expression patterns at the basic cellular level due to the hormonal input received via the endocrine system on the cell. Based on this logic, we should search for the type of diet that leads to optimal gene expression patterns, the problem is, these diet's will differ in various populations. Therefore, there is no one size fits all diet and this leads to controversy.

Fructose in large quantities (cokes, cakes, doughnuts)is bad because of the hostile hormonal environment it creates, the individual molecule and its fate as an energy source are harmless. Dietary fat in large quantities does not lead to same hostile hormonal environment (as long as it is not consumed in conjunction with excess fructose or glucose). If you don't believe me, check your fasting TAG's, then drink one coke a day for two weeks and recheck them. They will go up, why, because fructose metabolism by passes the rate limiting step in glycolosis which then shunts the energy to de novo lipogensis in the liver, but it also leads to hormonal changes that favor energy storage on a cellular level "ie insulin resistance, leptin resistance, etc" because the only time large quantities of fructose were available (unless your genetic heritage is from a tropical environments) was in the spring in summer when calories where in excess.

Your cells gene expression patterns change in response to the hormonal input received from large quantities of this effector molecule (fructose) and it paves the way for the ravenous hunger and eating paleolithic humans must have experienced in northern climates in the late spring and summer to pack on enough fat to survive the fall and winter.

Don't fool yourself into thinking large quantities of glucose and fructose vs large quantities of fat and protein don't tell our cells things about our environmental conditions. Through an evolutionary lens the various types of calories and the macronutrient ratios consumed in meals have profound implications on our body composition, hunger, and nutrient partitioning.

Various ratios are effectors that lead to specific types of hormonal milieu's which tell all cells (including the biggies, brain and liver) at lot about our current environmental conditions which will lead to changes behavior patterns and nutrient partitioning. Those that argue with this are arguing against evolution.

On a side note, Iron overload is a huge problem for males over the age of 30, you should strive to keep your serum ferritin around 30-50, Leo R. Zacharski, M.D. at Dartmouth has done all the research this topic. The long term health benefits of regular phlebotomy for males and post menopausal females are very real.

@ SanjeevI think the most likely explanation is, if you can get milk and tubers near at hand then walking to the forest (perhaps pushed back by your herds) and collecting fruit seems a low-yield thing not worth the effort and risk of conflict.And if you have a choice between fruit and honey, honey is the better score. And most of the group keep their hands free for defense if carrying back honey or meat.

Most people don't eat every edible thing in their environment and the reasons can be very complex.Group identity - avoiding a food an enemy eats - is probably why Jews don't mix milk and meat: this was the offering given to the idols of their rivals.(according to Maimonedes)

"If fructose is fattening due to its ability to become fat, then dietary fat should be even more fattening because it doesn't have to undergo an inefficient conversion process-- it's already fat. "

Stephan appears to be saying here that a calorie may not be a calorie, and that there "should be" a metabolic advantage from fructose.

Dietary fat and de-novo-from-fructose-in-the-liver fat are two very different phenomena. Let me boil down the difference:

1. Dietary fat comes with lots of friends. Vitamins A,D,K,E are some of them, but others might be CoQ10, AKG etc. All those are known to reduce and/or cure cardiovascular/metabolic syndromes in some people. Contrary, pure, refined, free fructose comes with nothing. Fructose from fruit comes with friends too which is one of the reasons it is better. Just to make things clear, similarly bad as refined fructose is refined fat - lets say margarine - and we know that already. Why don't we accept that refined fructose is also problematic at low levels, just like trans fats are ?

2. Dietary fat is mostly packed into the chylomicrons and is distributed via lymphatic system to the rest of the body. Fructose, almost entirely, goes to the liver to be converted into VLDLs and released. The problem: if there is a defect in beta oxidation or export pathway, this fat will start to accumulate in the liver:

http://www6.svsu.edu/~gmlange/BJLG04F10.pdf even with increased de novo lipogenesis, steatosis should only occur if storage of the lipids is increased due to abnormal exportation out of the hepatocyte or decreased utilization of the fatty acids in β-oxidation, suggesting that other mechanisms may also be involved in the deleterious effects of fructose on liver.

Accumulation of the fat in the liver is many times more problematic then accumulation in the adypocites, for obvious reasons.

3. Fructose DOES induce copper deficiency, this is pretty uncontroversial. This promotes cardiovascular problems. Fat doesn't. Copper deficiency might be a problem in some populations or groups.

4. Fructose is most potent AGE inducer. Fat could only temporary rise endotoxin levels on its side but that is quicly sorted out by immune system by adjusting the microbiota handling.

http://circ.ahajournals.org/content/114/6/597.fullTen times more fructose-derived AGEs form after 5 days than glucose-derived AGEs in vivo

5. Fructose, even in very small doses like 1 glass of soda could adversely influence gut flora. Its turbo fuel for most microbiota. Fat to my knowledge isn't really usable by microbiota, or when it is, these life forms prefer carbs anyway. There is huge number of people with some gut disorder who will benefit from reduced fructose and other carbs from FODMAPS. More, fructose is damaging to the immune system just like other carbs but is more potent (DOI: 10.4236/oji.2011.12005)

http://www.ncbi.nlm.nih.gov/pubmed/17217453

6. Fruit fructose comes with friends - quecertin and other flavonoids block GLUT receptors so fructose is not absorbed to the extent it is when those substances are removed by raffination. There are also some vitamins there. That might be the reason its safer.

Basically, its enough to get carbs from vegetables IMO. Fruit is far less damaging in moderation, but gives nothing over vegetables.

Dietary fat and de-novo-from-fructose-in-the-liver fat are two very different phenomena. Let me boil down the difference:

1. Dietary fat comes with lots of friends. Vitamins A,D,K,E are some of them, but others might be CoQ10, AKG etc. All those are known to reduce and/or cure cardiovascular/metabolic syndromes in some people. Contrary, pure, refined, free fructose comes with nothing. Fructose from fruit comes with friends too which is one of the reasons it is better. Just to make things clear, similarly bad as refined fructose is refined fat - lets say margarine - and we know that already. Why don't we accept that refined fructose is also problematic at low levels, just like trans fats are ?

2. Dietary fat is mostly packed into the chylomicrons and is distributed via lymphatic system to the rest of the body. Fructose, almost entirely, goes to the liver to be converted into VLDLs and released. The problem: if there is a defect in beta oxidation or export pathway, this fat will start to accumulate in the liver:

http://www6.svsu.edu/~gmlange/BJLG04F10.pdf even with increased de novo lipogenesis, steatosis should only occur if storage of the lipids is increased due to abnormal exportation out of the hepatocyte or decreased utilization of the fatty acids in β-oxidation, suggesting that other mechanisms may also be involved in the deleterious effects of fructose on liver.

Accumulation of the fat in the liver is many times more problematic then accumulation in the adypocites, for obvious reasons.

3. Fructose DOES induce copper deficiency, this is pretty uncontroversial. This promotes cardiovascular problems. Fat doesn't. Copper deficiency might be a problem in some populations or groups.

4. Fructose is most potent AGE inducer. Fat could only temporary rise endotoxin levels on its side but that is quicly sorted out by immune system by adjusting the microbiota handling.

http://circ.ahajournals.org/content/114/6/597.fullTen times more fructose-derived AGEs form after 5 days than glucose-derived AGEs in vivo

5. Fructose, even in very small doses like 1 glass of soda could adversely influence gut flora. Its turbo fuel for most microbiota. Fat to my knowledge isn't really usable by microbiota, or when it is, these life forms prefer carbs anyway. There is huge number of people with some gut disorder who will benefit from reduced fructose and other carbs from FODMAPS. More, fructose is damaging to the immune system just like other carbs but is more potent (DOI: 10.4236/oji.2011.12005)

http://www.ncbi.nlm.nih.gov/pubmed/17217453

6. Fruit fructose comes with friends - quecertin and other flavonoids block GLUT receptors so fructose is not absorbed to the extent it is when those substances are removed by raffination. There are also some vitamins there. That might be the reason its safer.

Basically, its enough to get carbs from vegetables IMO. Fruit is far less damaging, but gives nothing over vegetables.

One more thing related to unphysiologicall doses of fructose often used in animal research:

From Intermediary metabolism of fructosehttp://www.ajcn.org/content/58/5/754S.full.pdf

Of particular relevance to hepatic metabolism arc the concentrations of fructose likely to be attained in the hepatic portal vein. In humans (14) and baboons (8) maximal concentrations of 2.2 mmol/L have been recorded after a fructose or sucrose meal. We found values within the range 1.1-2.2 mmolfL, when fed or starved rats were given a large fructose meal by gastric intubation (4). In humans a maximum concentration of 1.0 mmol fructoscfL was recorded in peripheral blood (14). Because the normal blood fructose concentration is zero when no fructose is being absorbed, fructose concentrations in blood will vary from zero up to the maximum recorded above, according to the quantity in the diet.

So some of the conclusions of those papers could be applied postprandially in the context of portal vein and liver.

@SanjeevThat second paper you linked, 'Excessive Body Iron Stores Are Not Associatedwith Risk of Coronary Heart Diseasein Women', may not be quite what it seems. It depends on whether the measures of iron stores are accurate.

The authors of this paper entitled 'Ferritin Is Not an Indicator of Available Hepatic Iron Stores in Anemia of Copper Deficiency in Rats' http://www.clinchem.org/content/43/8/1457.full#F1

..found that copper deficient rats could have low serum ferritin but HIGH liver iron.

Without copper, iron is stuck in the liver and can't get to the bone marrow to make hemoglobin. So the rats had low hematocrit and ferritin, but high liver iron.

If this reflects what happens in humans, it means 'low iron stores' might actually mean high iron stores and copper deficiency in a significant number of people, possibly explaining the lack of correlation in the paper you linked.

OK, let me chime in here and explain what I meant with that asterisk, because it looks like some people are not getting my drift.

My comment was referring specifically to this line of reasoning that I've seen some people use: "fructose is fattening BECAUSE de novo lipogenesis converts it to fat in the liver".

For a person to become overweight or obese, the fat has to end up in fat cells-- you don't become overweight by accumulating liver fat alone. Therefore, the implication is that the liver converts fructose to fat, which travels to fat tissue and accumulates there.

Since only a fraction of fructose calories become fat, then if you accept this line of reasoning as true, then the implication is that dietary fat should be ~5X more fattening than fructose because it's already fat.

The reason I brought it up was to point out that this line of reasoning is obviously NOT correct.

The thing that matters is calories. If you eat extra fat, it gets shunted into fat tissue. If you eat extra glucose, it spares fat burning and the fat that wasn't burned gets shunted into fat tissue. If you eat extra fructose, it gets metabolized into glucose and fatty acids, which spare fat calories and the extra gets shunted into fat tissue.

That's my point. The body's ability to transform one energy source into another is irrelevant-- what matters is the total amount of energy coming in vs. leaving. The body finds a way to store the excess calories. This storage process may become less efficient at macronutrient extremes (i.e. very low-fat or very low-carb), but at almost all macronutrient proportions it's very efficient, and this has been repeatedly demonstrated in controlled trials.

Yes, exactly. I think somebody should tell Lustig about copper and iron. I came across a suggestion recently that obesity might be accompanied by iron overload in adipocytes. If it's true, it would explain everything: the oxidative stress and inflammation, the ER stress, and the calcium overload which according to Zemel, promotes lipogenesis and inhibits lipolysis.

Dr. Jeffrey Friedman, Dr. Rudolph Leibel, Dr. Jules Hirsch, Dr. Douglas Coleman, Dr. Michael Rosenbaum, Dr. Stephen O'Rahilly, Dr. Claude Bouchard are all saying the same thing: What we think is different about people who are obese is not what we THINK is is. We usually attribute it to ( lack of willpower, toxic environment)but is has a massive genetic underpinning.

Both Dr Leibel AND Dr. Friedman are trying to educate the public. This chronic disease is extremely complex and what we do not know could fill a vast ocean.

Also, Dr. Friedman's view when asked if there is any particular way of eating that is particularly fattening:

"The answer actually for people is NOT known and may be unanserable because of the difficulties of doing such studies.

I have a bias . My view is that a calorie is a calorie because they are all interconvertible in the body.

But, the PRECISE answer in people has never been tested. The reason all of these studies on diet are so difficult because typically you can get so few poeple to maintain the weight loss long term that you need enormous studies to see say show a difference between low carbohydrate and low fat diets. I have an opinion on thi s matter but here is no data that can really address it."

Dr. Leibel and Dr. Friedman are working together. They are both cream of the crop obesity researchers- the very best in the world

It seems to me that if we are to understand the genetics of diabetes, we must understand how these oscillations arise and how they get deranged. This is just as important in obesity as in diabetes, because adipocytes oscillate too.

'Free fatty acids (FFAs) and glycerol oscillate in plasma...These data show, for the first time, intrinsic lipolytic oscillations, which are glucose dependent and modulated by FFAs. We hypothesize that lipolytic oscillations are driven by oscillatory glucose metabolism...'http://www.ncbi.nlm.nih.gov/pubmed/15734837

In many kinds of cells, calcium oscillates between the endoplasmic reticulum where it's needed for protein folding, and the cytoplasm where it activates enzymes. Derangement of the oscillations means accumulation of unfolded proteins, which happens in many diseases, and transfer of the calcium to mitochondria, which they do not like.

Many other things oscillate with calcium, and one of them is ATP, whose synthesis requires magnesium or manganese. ATP activates the pumps that keep the calcium where it belongs. It follows that Mg and Mn in some sense control the oscillations.

Now as it happens, Mg and Mn also control DNA repair. Mutations are caused by failure of DNA repair, so the genetics of diabetes and obesity must therefore involve Mg and Mn in some way. You see where I'm going with this? If you feed people for several generations with carbohydrate foods from which Mg and Mn have been removed, you will get deranged cellular oscillations AND changes in DNA.

I hope Stephan will forgive me for delivering this lecture to Razwell on his blog.

When you hear blog commenters declare "Fructose leads to fatty liver!!", be wary and ask for details. The evidence is quite mixed, depending on what the control group is, the timeframe of the trial, etc.

Well, maybe, but look at the results table. Glucose actually led to very slightly more liver fat accumulation than did fructose. And a randomized trial, when moderately well-designed, is moderately telling.

"Participants in addition to a balanced weight-maintaining diet received 150 g of fructose or glucose/d for 4 weeks."

Since I changed from using sugar to using Truvia (in cooking, in tea ect) I've lost 5lbs - this was around a month ago. However this could also be because I've stopped getting sugar cravings so I might have started eating generally less of it anyway?

Really interesting post.The fat usually passes through the liver, is transported all over the body in different types of vesicles and will have different fats based on its chain length.Keep it Maintain through Dietpills

@RazwellI doubt if Friedman knows the whole story as I have described it. But I'm sure he knows about the problem of 'missing heritability', where a disease is very heritable according to twin studies, but you look everywhere for the genes and can't find them. Well, you do find a lot of genes, but with tiny effects.

The answer may lie in so-called junk DNA. This is highly repetitive DNA which evolves much faster than genes, and is now known not to be junk at all.

This DNA was recently found to bind and sequester certain transcription factors, meaning that it regulates gene expression. One of the transcription factors it binds is called C/EBP alphahttp://www.ncbi.nlm.nih.gov/pubmed/17526489

..which is very important in adipose tissue.http://www.ncbi.nlm.nih.gov/pubmed/7864870

This binding of transcription factors by junk DNA is so important that if it's disrupted in fruit flies, one body part can be transformed into another. So I think it's the place to look for the genetic component of obesity. I wonder if Friedman & co know about this.

What I mean that is that morbid obesity is an incredible complex phenomenoin with the unknowns being far greater than the knowns. Morbid obesity is NOT what we THINK it is ( e.g. willpower, toxic environment) Dr. Leibel went out of his way to say this.

Dr. Leibel has 30 years researcing this. And he has conducted some of the very best research on this. Extreme detail. Dieting wreaks HAVOC ( all hell breaks loose in Dr. Leibel's own words ) on your body and the effects do NOT go away so far as Dr. Leibel can tell.

What do well knmown Internet guru scammers promote? That's right, dieting. Anybody who promotes dieting is scientifically illiterate, or they are a deliberate opportunist making money off of and exploiting fat people.

The most recent research from Dr. Rudolph Leibel demonstrates this very soundly. I am on extremely firm scientific ground.

There is another bad effect of dieting that you can add to the list - making food VERY palatable at your new dieted down weight.

Dieting is a complete failure and needs to be discarded forever immediately.

Hi, Jane

If Dr. Friedman does not know it or has not explored it it is likely somebody like Dr Rosenbaum or Dr Leibel has.

Fructose ( or sugar, or fat, ... ) is not inherently fattening outside of a diet that has too many calories for the individual. I don't think that is complicated of controversial, but too often people need to be reminded of this fact. They start to confuse the how ( diet choices ) with the why ( weight change ) without scientifically isolating for the causative variable ( calories ).

The questions should focus on what chemical, cultural, and genetic properties cause someone to habitually overconsume calories and what steps can be realistically taken to change those forces.

I then leapt beyond my mattress to look Air swimmers soothe your ex. I noticed they wanted to be snuggled Remote controlled flying therefore i introduced your pet to sleep with me Radio controlled fish. The subsequent slumber above,Flying fish toy my mother place your pet to settle in his crib and once he or she drifted off My spouse and i scooped him upward and also introduced him to sleep with me at night.

Hi. My son is fructose intolerant. He continued to loose weight and had stomach issues daily. Both hfcs and fruit fructose upsets his body. I started a blog about this topic because I couldn't find enough info abut it. Thank you for studying hfcs and obesity and heart disease. So important. WHat about natural fructose? In my son's body it causes horrible problems- and why does everything contain hfcs?!! Even the wheat bread we were eating- it's crazy! http://fructoseandbellyachefree.blogspot.com/

Very interesting and we need lots more research into these crucial issues and many more proper studies.

The trouble is for some of us sugar and fructose are like cocaine and alcohol. We have no switch off mechanism for them. I can easily eat 1000 calories of raisins in one go or 8 bananas or massive quantities of fruits as they give me a sugar high. So even if a small amount is okay if you are an addict you cannot do small - you eat and eat and eat and it is truly horrible so total abstinence is the only way.

Not only do we eat what is there but we drive out in cars on long journeys to buy or even sometimes to pick in my case garden plums in season in massive quantities the addictive substance. So although I pretty much agree if your diet is healthy and you have a few processed things you're probably okay for addicts we just cannot do that. Sugar addicts are often the children of alcoholics and we have a different biochemistry. It is a massive burden to bear and I hate it.

About Me

I'm a writer and science consultant with a background in neuroscience and obesity research. I have a BS in biochemistry and a PhD in neurobiology. I'm the author of "The Hungry Brain: Outsmarting the Instincts That Make Us Overeat".

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